Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)

• Status: Completed
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This study seeks to (i) determine a safe and tolerated dose of CYT387 (momelotinib) given to patients with PMF, post-PV or post-ET and, (ii) assess the effectiveness of orally-administered CYT387 as a treatment for PMF, post-PV or post-ET.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences; Sierra Oncology, Inc.
• Treatments: N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Criteria

Inclusion Criteria:

• Diagnosis of PMF or post-polycythemia Vera (PV) or post-essential Thrombocythemia (ET) MF as per revised World Health Organization (WHO) criteria.

• High-risk or Intermediate-2 risk MF (as defined by the International Prognostic Scoring System [IPSS]; Appendix 13.6); or intermediate-I risk MF (IPSS) associated with symptomatic splenomegaly/hepatomegaly and/or unresponsive to available therapy.

• Must be at least 18 years of age with life expectancy of ≥ 12 weeks.

• Must be able to provide informed consent and be willing to sign an informed consent form.

• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

• Must have evidence of acceptable organ function within 7 days of initiating study drug as evidenced by the following:

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5 x ULN if in the investigator's opinion the elevation is due to extramedullary hematopoiesis)

• Bilirubin ≤ 2.0 x ULN or direct bilirubin < 1.0

• Serum creatinine ≤ 2.5 x ULN

• Absolute neutrophil count ≥ 500/µL

• Platelet count ≥ 50,000/µL

• Females of childbearing potential must have a negative pregnancy test within 4 days of initiating study drug.

Exclusion Criteria:

• Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide), immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin) within 14 days prior to initiation of study drug.

• Incomplete recovery from major surgery within four weeks of study entry.

• Radiation therapy within four weeks of study entry.

• Women of childbearing potential, unless surgically sterile for at least 3 months (ie, hysterectomy), OR postmenopausal for at least 12 months (FSH > 30 U/mL), OR unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.

• Men who partner with a woman of childbearing potential, unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through to the end of study. Permitted methods for preventing pregnancy must be communicated to study subjects and their understanding confirmed.

• Females who are pregnant or are currently breastfeeding.

• Known positive status for HIV.

• Clinically active hepatitis B or C.

• Diagnosis of another malignancy unless free of disease for at least three years following therapy with curative intent. Patients with early-stage basal cell or squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in situ or superficial bladder cancer may be eligible to participate at the Investigator's discretion.

• Any acute active infection.

• Cardiac dysrhythmias requiring treatment, or prolongation of the QTc (Fridericia) interval to > 450 msec for males or > 470 msec for females at prestudy screening, unless attributable to pre-existing bundle branch block.

• Presence of ≥ Grade 2 peripheral neuropathy.

• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), uncontrolled or unstable angina, myocardial infarction, cerebrovascular accident, or pulmonary embolism within 3 months prior to initiation of study drug.

• Uncontrolled inter current illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.